Structural Bioinformatics to Unveil Weaknesses of Coronavirus Spike Glycoprotein Stability

Bongini, P.; Trezza, A.; Bianchini, M.; Spiga, O.; Niccolai, N.

Alternative strategies for developing antiviral drugs are needed, as vaccines could not be the final answer against the present SARS CoV-2 outbreak, due to the still existing ambiguities in the immunological response to the virus. Thus, SARS CoV-2 enzymes have been thoroughly investigated to develop their inhibitors as antiviral drugs. We have searched the latter antiviral drugs among those small molecules that can interfere with the trimeric assembly of the S glycoprotein. We have systematically explored the trimer interfaces in the search of pockets that can be suitable for ligand binding. Virtual screening of FDA-approved drug library confirmed that concave moieties of S glycoprotein protomer interfaces can act as binding sites of small molecules. Interfering with S glycoprotein quaternary assembly, these small molecules would represent an alternative family of antiviral drugs.